Project Summary/Abstract: Cancer Imaging and Radiobiology (CIR) The goal of the Cancer Imaging & Radiobiology (CIR) Program is to realize technology innovations that promote, foster and underpin translational research in the detection, diagnosis, treatment and therapeutic monitoring of solid cancers and human health status following radiation exposure. The group utilizes biophysical and engineering approaches and methods to develop and improve imaging, measurement, and treatment technologies that aid in understanding the biological and physiological processes that are indicators of the growth, progression and regression of cancer in diagnostic and therapeutic settings. CIR members seek to achieve these goals by conducting research addressing 3 themes: (1) Cancer Nanotechnology to deliver and excite targeted magnetic nanoparticles for treatment of loco-regional and potentially metastatic cancers, (2) Electron paramagnetic resonance (EPR) in Radiation Dosimetry to quantitate radiation exposure, and (3) Imaging and Image-Guidance in Cancer Investigations to develop molecular and physically-based imaging and image-guided techniques for cancer detection, characterization and surgery or other interventions. CIR has 22 members from 10 departments holding $17.8M in peer-reviewed funding (total costs, with $4.0M from NCI, 25%) which includes multi-project support for the Dartmouth Center for Cancer Nanotechnology Excellence (U54-CA151662), the Dartmouth Physically-Based Biodosimetry Center for Medical Countermeasures against Radiation (U19AI091173), and the Center for Surgical Innovation for Translational Research at Dartmouth (C06- RR030432). CIR's publication record over the previous 5-year funding period exceeds 317 cancer-related contributions to the peer-reviewed literature (10% [31] in leading journals), with intra- and inter-programmatic publication rates of 60% (189) and 20% (64), respectively. All 22 members are co-authors on intra-programmatic publications, and 20 are co-authors on inter-programmatic. These data are indicative of an innovative, productive, and highly interactive cancer-focused program. During the current funding period, CIR members have been responsible for publishing the first evidence that (i) passive bioelectrical properties discriminate high and low-grade prostate adenocarcinoma, (ii) breast tumor response to neoadjuvant chemotherapy can be determined within the first 4 weeks of initiation of treatment with diffuse near-infrared spectral tomography, (iii) ALA-induced PpIX accumulates with diagnostically-significant levels of fluorescence in low-grade glioma, (iv) multiple nanoparticle bound states can be concurrently quantified with Magnetic Particle Imaging of Brownian motion, (v) dual tracer fluorescence spectroscopy enables quantitative molecular imaging of tumor receptor binding of targeted diagnostic and therapeutic agents, (vi) finger and toenails can be used as practical individualized radiation dosimeters, and (vii) Cherenkov radiation dose can be measured in breast cancer patients via fluorescence imaging. CIR provides an innovative framework, facilitated through NCCC support, for investigating new approaches to identify and manage cancer in patients and radiation exposure in survivors.